1. Field of the Invention
The present invention relates to a method for angiogenesis inhibition, neoplasm depression or immunostimulation. etc. which comprises administering to a person or an animal anhydrous glutamic acid, pyroglutamic acid, or derivative thereof as active ingredient.
2. Prior Art
A vascular-related disease includes, for example, propagation and transition of neoplasm, inflammation, rheumatoid arthritis, diabetic retinopathy, and psoriasis, and it is greatly related with angiogenesis and immune function. Angiogenesis is phenomenon of generating new capillary blood vessels in animal tissues or organs, in the process of which, vascular basement membrane is disassembled and attacked by protease, vascular endothelial cell is grown by migration and bonded to extra cellular matrix, vascular endothelial cell is differentiated, and vascular cavity is formed. In general, new blood vessels are formed and extended in childhood and growth period. However, when growth period is past, the occasion of angiogenesis in the body is limited. Angiogenesis is observed under normal physiology condition such as luteinization, ovulation, embryogenesis, and placentation, and also occurred in cure process of lesion and resealing process of inflammation. As described above, angiogenesis occurs in normal state and has an important role in restoration of tissues, but it is known that capillary increases in a lot of chronic diseases such as diabetes mellitus and that angiogenesis causes grave lesion to tissues.
Angiogenesis is involved in etiology and aggravation of case of various diseases. The diseases include enhancement and transition of malignant, diabetic retinopathy, neovascular glaucoma, inflammatory dermatosis, joint fluid rheumatism, osteoarthritis, atherosclerosis, and obstructive affection such as myocardial infarction.
For example, when malignant tumor multiplies, tumor cell induces vascular neogenesis for itself by angiogenesis promoter to get nourishment and oxygen which are necessary for propagation of tumor cell, and tumor cell further grows while getting nutrient through new blood vessels. Transition of tumor cell to other organ and site also induces angiogenesis, and tumor cell is carried by the bloodstream. In the case of diabetic retinopathy, capillary is clogged up because of the viscosity blood set up by diabetes mellitus and is affected, and bleeding and edema are produced in retina. When bleeding and edema are chronic, the retina falls short of oxygen and nourishment, and then newborn blood vessel originates on the retina or nervous system mammilla so that fiber tissue is formed circumferentially. The retina is pulled by means of the fiber tissue (retinal detachment) or the retinal blood vessel is occurred bleeding (vitreous hemorrhage), and then serious visual handicap or blindness is occurred before long.
As described above, because angiogenesis is deeply involved in the onset and development of various diseases, a lot of searches of materials inhibiting angiogenesis have been done hitherto and investigation is pushed forward at the present zealously as an aim in a treatment or prevention of these diseases. As material and drug with action inhibiting angiogenesis, sulfation polysaccharide (Japanese Patent Laid-Open No. S63-119500 bulletin), trafermin, heparin and steroid (U.S. Pat. No. 4,994,443 specification; or U.S. Pat. No. 5,001,116 specification), ascorbic acid ether and this related-compound (Japanese Patent Laid-Open No. S58-131978 bulletin), interferon alpha or interferon beta (Sidky et al., “Cancer Research”, 47:5155-5161, (1987)), thiazole derivative (Japanese Patent Publication No. H6-62413 bulletin), shark cartilage extract (chondroitin and mucopolysaccharide) (Japanese Patent Laid-Open No. H10-147534 bulletin), polysaccharide derived from streptococcus bacteria (Japanese Patent Publication No. H6-62426 bulletin), O-displacement fumagillol derivative (Japanese Patent No. 3120187 bulletin), neo agarose oligosaccharide (Japanese Patent No. 3071068th bulletin) etc. are proposed.
However, considering practical side, all of the materials having action of angiogenesis inhibition proposed or examined till now as a material did not show the sufficiently satisfied effect. The materials were used based on experimental findings under the dosage condition that is not practical, the materials had worries about adverse reactions, or the materials must be administered in high doses in use. Therefore, the development of materials by which angiogenesis is inhibited more effectively and materials to be used without any worry in a point of safety is demanded.